The Department of Defense office of the Congressionally Directed Medical Research Programs (CDMRP) has recommended a Hearing Restoration Research Program (HRRP) Focused Research Award to Dr. Samson Jamesdaniel for studying hearing loss induced by environmental exposures. Acquired hearing loss is the third-most common chronic physical condition among American adults after hypertension and arthritis, and the worldwide prevalence is estimated to double by 2050. Therefore, there is a critical need to discover effective prevention and treatment strategies, which are contingent upon understanding the underlying mechanisms. With the support of this grant, Dr. Jamesdaniel’s research team will investigate the nitrative stress mechanism underlying hearing loss induced by concurrent exposure to noise and heavy metal lead, which are pervasive risk factors in the military as well as the urban environment. The aims of this project are to: (1) elucidate the association between inner ear protein nitration and noise- and/or lead-induced nerve damage and hearing loss and (2) evaluate the efficacy of targeting nitrative stress for mitigating noise- and/or lead-induced inner ear damage and hearing loss. This research is expected to yield a detailed understanding of how combined exposure to noise and lead induces overt and hidden hearing loss by regulating the nitration of inner ear proteins and determine the therapeutic value of targeting a shared signaling pathway. These contributions will provide new knowledge about the harmful interactions of chemical and physical stressors on hearing and will have important translational applications in mitigating hearing loss induced by noise and lead exposures. As there are no FDA-approved drugs to treat sensory neural hearing loss, evaluating the otoprotective efficacy of compounds that target nitrative stress will address a critical need. The title of the research project is “Targeting nitrative stress for mitigating hearing loss induced by concurrent ototraumatic exposures.”